Structural biology of viruses

Size: px

Start display at page:

Download "Structural biology of viruses"

Dwayne Waters
6 years ago
Views:

1 Structural biology of viruses Biophysical Chemistry 1, Fall 2010 Coat proteins DNA/RNA packaging Reading assignment: Chap. 15

2 Virus particles self-assemble from coat monomers Virus Structure and Function 451 FIGURE 15.1 Schematic drawings of virus particles. Left: Poliovirus, a simple icosahedral virus with a diameter of about 300 Å (based on a crystal structure). Right: Flavivirus, an enveloped virus with a crystal diameter of about 470 Å (based on a cryo-em model with models of coat protein molecules from a crystal structure fitted into the cryo-em density). The colors denote subunits in different environments as discussed below. From VIPER ( membrane proteins themselves or with an inner symmetric protein layer. Nonenveloped viruses normally have either helical or icosahedral symmetry. Some

Icosahedral coats are the most common ones 452 A Textbook of Structural Biology FIGURE 15.2 An icosahedron showing the positions of the five-, three- and two-fold symmetry axes.

3 Icosahedral coats are the most common ones 452 A Textbook of Structural Biology FIGURE 15.2 An icosahedron showing the positions of the five-, three- and two-fold symmetry axes. The repeated unit is marked in gray. This is only one of many possible choices of the repeated unit. The basis of the theory is that it is possible to form six-fold and five-fold interactions with similar contacts between subunits. A plane triangular net with six-fold contacts can be transformed into an icosahedron if some of the six-fold contacts are replaced by five-fold contacts in a regular manner. The five-fold contacts create curvature, and depending on the position of these five-fold axes, icosahedra with different numbers of triangles are formed. Caspar and Klug

4 Interactions can be viewed in two dimensions Virus Structure and Function 453 FIGURE 15.3 Triangular nets where points of six-fold symmetry have been selected in a regular T = 1 T = 7 T = 3 T = 4 k 1, 2 1, 1 1, 0 2, 0 h

Various triangulation numbers 454 A Textbook of Structural Biology FIGURE 15.4 Viruses with triangulation numbers 1, 3, 4, 7 and 13 showing their relative sizes.

5 Various triangulation numbers 454 A Textbook of Structural Biology FIGURE 15.4 Viruses with triangulation numbers 1, 3, 4, 7 and 13 showing their relative sizes. The surface of the virus particles is shaded according to its distance from the center, darker being closer. Some particles have an icosahedral shape, but the particles all have icosahedral symmetry. The drawings are based on the crystal structures (from left to right) of satellite tobacco necrosis virus, phage MS2, Nudaurelia capensis ω virus, phage HK97 and the bluetongue virus. From VIPER (

metry. The drawings are based on the crystal structures (from left to right) of satellite tobacco necrosis virus, phage MS2, Nudaurelia capensis ω virus, phage HK97 and the bluetongue virus.

6 metry. The drawings are based on the crystal structures (from left to right) of satellite tobacco necrosis virus, phage MS2, Nudaurelia capensis ω virus, phage HK97 and the bluetongue virus. From VIPER ( Virus particles self-assemble from coat monomers FIGURE 15.5 The jellyroll fold in a viral coat protein subunit (satellite tobacco necrosis virus, PDB: 2BUK). viruses are mainly responsible for the shape and size of the virus particles and are able to form five-fold, three-fold and two-fold contacts. When multiples of 60 chemically identical subunits form the shell, the molecules must be able to form at least slightly different contacts in a correct way to make well-ordered capsids with icosahedral symmetry. The first structures of virus particles to be

Interdigitation often stabilizes coats 456 A Textbook of Structural Biology FIGURE 15.7 The arrangement of 18 subunits around the three-fold (quasi-six-fold) axis in the southern cowpea mosaic virus.

7 Interdigitation often stabilizes coats 456 A Textbook of Structural Biology FIGURE 15.7 The arrangement of 18 subunits around the three-fold (quasi-six-fold) axis in the southern cowpea mosaic virus. The partially ordered arm in one of the subunits (marked in red) interacts with arms from symmetry-related subunits at the three-fold axis (beta annulus, indicated with an arrow). In this virus, the N-terminal 23 amino acids are disordered in all subunits. This region contains several positively charged residues and probably interacts with the viral RNA, which is asymmetric.

8 Cell entry: hemagglutinins A Textbook of Structural Biology

9 Cell entry: simple viruses Virus Structure and Function 459 FIGURE 15.9 The E1 protein from the Semliki Forest virus, an alphavirus (PDB: 1I9W). The coloring is from N-terminal (blue) to C-terminal (red). The fusion peptide is the loop at the extreme right of the molecule and is hidden through contacts to another protein in a homodimer. The anchor to the viral membrane is at the C-terminus of the protein, but this part of the protein was removed before crystallization and is therefore not seen here. in the host cell that allows the particle or the viral genome to pass through the cellular or endosomal membrane. Picornaviruses, including poliovirus and rhinovirus (the common cold virus), are simple viruses with only a few structural and non-structural proteins. Their entry mechanisms have been studied as one of the possible ways of finding drugs to prevent viral infections. The mature poliovirus parti-

Cell entry: poliovirus architecture A Textbook of Structural Biology FIGURE 15.10 N-terminal arms in the poliovirus. Left: The repeating unit (protomer) as seen from the inside of the shell.

10 Cell entry: poliovirus architecture A Textbook of Structural Biology FIGURE N-terminal arms in the poliovirus. Left: The repeating unit (protomer) as seen from the inside of the shell. The N-terminal extensions are shown in dark shading, while the main part of the subunit is pale. The N-termini of VP1 and VP3 are bound to the main parts of VP3 and VP1, respectively, while the remaining N-terminal of VP2, after cleavage of VP4, is bound to the subunit itself. Right: Packing of subunits around the five-fold axis as seen from the

FIGURE 15.11 The MS2 coat protein dimer as seen in a radial direction from the outside of the Getting particle.

12 The binding of the RNA hairpin by the MS2 dimer (PDB: 1ZDI).

11 FIGURE The MS2 coat protein dimer as seen in a radial direction from the outside of the Getting particle. the A segment right of bound RNA back is shown into (purple) the (PDB: virus 2BU1). FIGURE The binding of the RNA hairpin by the MS2 dimer (PDB: 1ZDI). Adenine bases 10 and 4 are bound in corresponding pockets in the two monomers of the dimer, and uracil base 5 is stacked to a tyrosine sidechain in one of the subunits. To the right, the secondary structure of the hairpin is shown. The initiation codon of the replicase subunit is boxed.

12 component Genomeis packaging added turn. inthe bacteriophage head is assembled using scaffolding proteins that (a) (b) Head containing DNA Collar Tail tube Tail sheath Long tail fibers Base plate with short tail fibers FIGURE Phage T4. To the left is an electron micrograph of the phage (courtesy of R. Duda, Pittsburgh). The main parts of the virion are labeled in the schematic view to the right.

13 Some details of the packing apparatus Virus Structure and Function 463 FIGURE The trimeric gp5-gp27 complex. The three monomers of gp5 are in red, blue and yellow, and the monomers of gp27 in green, brown and purple. The lysozyme domain of gp5 is at the upper part of the triple beta helix that forms the stalk of the molecule.

The T4 baseplate FIGURE 15.14 The trimeric gp5-gp27 complex. The three monomers of gp5 are in red, blue and yellow, and the monomers of gp27 in green, brown and purple.

The gp5- gp27 complex is at the center of this model. gp5 is in yellow and gp27 (barely visible) in turquoise.

14 The T4 baseplate FIGURE The trimeric gp5-gp27 complex. The three monomers of gp5 are in red, blue and yellow, and the monomers of gp27 in green, brown and purple. The lysozyme domain of gp5 is at the upper part of the triple beta helix that forms the stalk of the molecule. FIGURE Fitting of several proteins from the T4 baseplate into a cryo-em map. The gp5- gp27 complex is at the center of this model. gp5 is in yellow and gp27 (barely visible) in turquoise. The other proteins that are modeled are gp9 (blue), gp8 (red), gp11 (orange), and gp12 (purple). (Courtesy of Thomas Goddard, University of San Francisco.) are degraded and leave before a portal protein injects the DNA. The tail is assembled separately and joined to the DNA-packed head. In the mature virion, the tail is loaded like a spring. Interactions between the short tail fibers and the bacterium lead to conformational changes in the baseplate.

Proteins and symmetry

Proteins and symmetry Viruses (symmetry) Viruses come in many shapes, sizes and compositions All carry genomic nucleic acid (RNA or DNA) Structurally and genetically the simplest are the spherical viruses